Claudin-1 expression is induced by tumor necrosis factor-alpha in human pancreatic cancer cells.
Claudin-1 is a membrane protein with four transmembrane domains, that is exclusively localized at cellular tight junctions. Recent studies have reported that claudin-1 plays an important role in cancer invasion and metastasis. However, the significance of claudin-1 in pancreatic cancer is still unknown. In the present study, we investigated the role of claudin-1 expression in pancreatic cancer growth using the PANC-1 human pancreatic cancer cell line. Treatment with tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, resulted in increased detection of 89 kDa products of poly-(ADP-ribose) polymerase (PARP), a marker of apoptosis, and decreased PANC-1 cell proliferation by 23%. Expression of claudin-1 was up-regulated by TNF-alpha in a concentration-dependent manner in PANC-1 cells. PANC-1 cells treated with TNF-alpha and siRNA against claudin-1 showed a 15% increase in proliferation; i.e. the cells transfected with siRNA against claudin-1 showed resistance to TNF-alpha-induced apoptosis. These results suggest that claudin-1 expression is responsible for TNF-alpha-dependent growth signals and the proliferation of pancreatic cancer cells.
Kondo
Jun
J
Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Sato
Fuyuki
F
Kusumi
Tomomi
T
Liu
Yang
Y
Motonari
Ohashi
O
Sato
Tatsusuke
T
Kijima
Hiroshi
H
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D062445:Claudin-1; D024161:Collagen Type XI / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
C568108:CLDN1 protein, human; C499319:COL11A2 protein, human; D062445:Claudin-1; D024161:Collagen Type XI; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha